Hydraulically Actuated Pump for Fluid Administration

ABSTRACT

A fluid delivery device comprises a hydraulic pump chamber having a hydraulic fluid. A fluid reservoir is coupled to the hydraulic pump chamber and is configured to contain a fluid deliverable to a patient. A first actuator is coupled to the hydraulic pump chamber and is configured to pressurize the hydraulic pump chamber and configured to transfer energy through the hydraulic pump chamber to the fluid reservoir. A second actuator is coupled to the hydraulic pump chamber and is configured to pressurize the hydraulic pump chamber and configured to transfer energy through the hydraulic pump chamber to the fluid reservoir.

REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.12/762,307, filed on Apr. 17, 2010, which is a continuation of U.S.application Ser. No. 12/336,363 (now U.S. Pat. No. 8,070,726), filed onDec. 16, 2008, which is a continuation of U.S. application Ser. No.10/831,354 (now U.S. Pat. No. 7,530,968), filed on Apr. 23, 2004, whichclaims the benefit of U.S. Provisional application 60/465,070, filed onApr. 23, 2003, all of which are incorporated herein by reference intheir entirety.

BACKGROUND OF THE INVENTION

The systems and methods described herein relate to a hydraulic pumpsystem that can be used in medicament pumps for injectables,specifically to low-cost, miniature, single-use pump systems.

Various people, such as diabetics, require continuous or near continuousinfusion of certain drugs or medicines (broadly referred to herein asmedicaments).

Many attempts have been made to provide continuous or near continuousdosing of medicaments, such as insulin, using pump systems. For example,one known pumping technique uses gas generated by various means toadvance a plunger in a syringe, thereby injecting the medicament throughan infusion set. The infusion sets is a means for conveying medicamentthrough the patient skin and may comprise a standard needle, amicroneedle, a microneedle array, and a catheter and cannula system.

Although these systems can work quite well, patients using thesesystems, particularly in continuous dose mode, need to monitor closelyor deactivate these devices under circumstances where the ambient airpressure may vary greatly, such as in an airplane. In particular,patients need to be careful that the infusion pump does not deliver adangerously increased dosage in airplanes at high altitudes, where theambient pressure is significantly reduced.

What is needed is a simple, inexpensive, single-use only medicament pumpsystem. Such a system must have the capacity to provide variable dosingunder patient control as well as safety and consistency in the metereddose at any range of ambient pressures or operating conditions.

SUMMARY

In an exemplary embodiment, the systems described herein include, interalia, a pump device, which may be single use, and that provides forsustained low volume (preferably high potency) medicament application,such as for use by insulin-dependent diabetics and other patients. Thepump may employ as an actuator a spring-compressed bellows crank, hingedplate, paired roller set, or other peristaltic mechanisms to force avolume of hydraulic fluid through a flow restrictor, such as anaperture, thereby expanding one chamber of a two chamber hydrauliccylinder. The second (fluid storage) chamber, containing a medicament,is vented through a conventional orifice as the hydraulic chamber isexpanded by introduction of additional hydraulic fluid. The medicamentthus expelled may then be injected or infused into a patient via anysuitable injection and/or infusion mechanism.

The restrictor, in one embodiment, may be a hydraulic fluid aperture andmay be a fixed micro-aperture of approximately 0.1-10 μm in diameter, orabout 1-5 μm in diameter, and one ten-thousandths of an inch (0.0001″,or about 2.5 μm) in diameter. In another embodiment, the hydraulic fluidaperture may be an adjustable aperture providing either continuous oratep-wise diameter variations of approximately 0.1-10 μm in diameter, orabout 1-5 μm in diameter, preferably one ten-thousandths of an inch(0.0001″, or about 2.5 μm) in diameter. Combined with a hydraulic fluidof appropriate viscosity, the micro-aperture provides precise pressureregulation that is insensitive to ambient pressure or otherenvironmental conditions. This insensitivity, in turn, allows for highlyaccurate dosing and dose regulation under a wider range of conditionsthan previously seen in the arts.

Thus one aspect of the invention provides a hydraulically actuated fluiddelivery system for sustained delivery of a liquid component,comprising: a pump chamber, and a fluid storage chamber having anorifice and being functionally connected to said pump chamber by amoveable barrier; a hydraulic fluid reservoir for storing a highviscosity fluid, said reservoir being connected to said pump chamber,via a restrictor, such as an aperture, which may be less than 10 μm indiameter, and the largest insoluble particle, if any, in said hydraulicfluid may optionally be no more than the size of said aperture; and, anactuator functionally connected to said hydraulic fluid reservoir tocause said hydraulic fluid to flow into said pump chamber through saidaperture, thereby expanding the volume of said pump chamber, displacingsaid moveable barrier and causing a quantity of said liquid componentstored in said fluid storage chamber to be delivered at a sustainedrate.

In one embodiment, the pump chamber and the fluid storage chamber areboth within a compartment.

In one embodiment, the moveable barrier is a piston or plunger plate.

In one embodiment, the movement of the piston or plunger plate is guidedsuch that the piston or plunger plate does not flip or generate leakagewhen moving.

In one embodiment, the moveable barrier is one or more deformablemembranes separating the pump and the fluid storage chambers.

In one embodiment, the liquid component is a medicament, and the wall ofthe fluid storage chamber is composed of bio-inert materials.

In one embodiment, the aperture has a fixed size.

In one embodiment, the aperture is adjustable in size to allow variablehydraulic pressure.

In one embodiment, the size of the aperture is adjusted by a thumbwheelcontrol/dial.

In one embodiment, the thumbwheel control activates a miniaturized valveor iris device.

In one embodiment, the quantity of said liquid component is expelled ata rate selected from: about 100 nl-1 μl per minute, about 1-10 μl perminute, or about 10-100 μl per minute.

In one embodiment, the actuator is a miniaturized bellows crank, pairedrollers, one or more piezoelectric elements, a ratchet or stepper motordriven unit, a two-plate hinged peristaltic mechanism, an electricallydriven or piezoelectric mechanism.

In one embodiment, the actuator employs one or more external springshaving a constant spring coefficient over its full range of motion.

In one embodiment, the fluid delivery system further comprises aconnective passage linking the hydraulic fluid reservoir to the pumpchamber through the aperture.

In one embodiment, the liquid component is a solution of a medicament.

In one embodiment, the medicament is insulin, an opiate, a hormone, apsychotropic therapeutic composition.

In one embodiment, the orifice of the fluid storage chamber is connectedto an infusion set for delivering the liquid component to a patient.

In one embodiment, the patient is a mammalian patient selected fromhuman or non-human animal.

In one embodiment, the infusion set is a needle, a lumen and needle set,a catheter-cannula set, or a microneedle or microneedle array attachedby means of one or more lumens.

In one embodiment, the pump is manufactured with inexpensive materialfor single-use.

In one embodiment, the inexpensive material is latex-free and issuitable for use in a latex-intolerant patient.

In one embodiment, the inexpensive material is disposable or recyclable.

In one embodiment, the inexpensive material is glass or medical gradePVC.

In one embodiment, the fluid delivery system further comprises a secondhydraulic reservoir.

In one embodiment, the second hydraulic reservoir is separately andindependently controlled by a second actuator.

In one embodiment, the second hydraulic reservoir and the originalreservoir are both connected via a common connective passage and throughthe aperture to the pump chamber.

In one embodiment, the second hydraulic reservoir is connected to thepump chamber through a second aperture.

In one embodiment, one of the two hydraulic reservoirs is used forsustained delivery of the liquid component, and the other of the twohydraulic reservoir is used for a bolus delivery of the liquid componentat predetermined intervals.

In one embodiment, both apertures are independently adjustable.

In one embodiment, one of the two apertures are adjustable.

In one embodiment, the sustained delivery is over a period of: more than5 hours, more than 24 hours, more than 3 days, or more than one week.

In one embodiment, the viscosity of the hydraulic fluid is at leastabout ISO VG 20, or at least about ISO VG 32, or at least about ISO VG50, or at least about ISO VG 150, or at least about ISO VG 450, or atleast about ISO VG 1000, or at least about ISO VG 1500 or more.

Another aspect of the invention provides a hydraulically actuated pumpsystem comprising: a pump chamber functionally connected to a moveablebarrier; a hydraulic fluid reservoir for storing a high viscosity fluid,said reservoir being connected to said pump chamber via an aperture ofless than 10 and in some embodiments less than 3 m in diameter, and thelargest insoluble particle, if any, in said hydraulic fluid is no morethan the size of said aperture; and, an actuator functionally connectedto said hydraulic fluid reservoir to cause said hydraulic fluid to flowinto said pump chamber through said aperture, thereby expanding thevolume of said pump chamber, displacing said moveable barrier.

Another aspect of the invention provides a method of administering amedicament, comprising: compressing a hydraulic fluid reservoir to forcesaid hydraulic fluid through a connection means; passing said hydraulicfluid through an adjustable aperture into a pump chamber, wherein saidpump chamber is separated from an adjacent fluid storage chamber by amoveable barrier and wherein said fluid storage chamber is filled with amedicament; displacing said moveable barrier into said fluid storagechamber by filling said pump chamber with said hydraulic fluid, whereinsaid displacing causes a quantity of said medicament to be expelled fromsaid fluid storage chamber through an output orifice.

In one embodiment, the passing is regulated by the adjustable aperturevarying the flow of the hydraulic fluid and thus the quantity of themedicament expelled through the orifice.

In one embodiment, the method further comprises injecting a quantity ofthe medicament into a patient through an infusion set connected to theorifice.

In one embodiment, the compressing employs peristaltic compaction of thereservoir at a constant rate.

In one embodiment, the compressing employs peristaltic compaction of thereservoir at a variable rate.

In one embodiment, the method further comprises rapidly compressing asecond hydraulic reservoir fluidly connected to the pump chamber todisplace the moveable barrier and thus cause a bolus of the medicamentto be expelled through the orifice.

In one embodiment, the method further comprises passing the hydraulicfluid from the second hydraulic reservoir through a second aperture intothe pump chamber.

It should be understood that the individual embodiments described aboveare meant to be freely combined with one another, such that anyparticular combination may simultaneously contain two or more featuresdescribed in different embodiments whenever appropriate. In addition,all embodiments described for one aspect of the invention (such asdevice) also applies to other aspects of the invention (e.g. method)whenever appropriate.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure may be better understood and its numerousfeatures and advantages made apparent to those skilled in the art byreferencing the accompanying drawings.

FIG. 1 is a high-level functional schematic drawing of a hydraulic pumpsystem, according to one embodiment of the invention.

FIG. 2 is a high-level functional schematic drawing of a fluid deliverysystem comprising the hydraulic pump system, according to one embodimentof the invention.

FIGS. 3A-3B are schematic drawings illustrating one of the advantages ofthe fluid delivery system comprising the hydraulic pump system.

FIGS. 4A-4C are high-level functional schematic drawings of severalfluid delivery system with various barriers.

FIG. 5 is a high-level functional schematic drawing of an alternativefluid delivery system, according to one embodiment of the invention. Thealternative fluid delivery system in this embodiment features arrayedmicroneedles on an transdermal patch.

FIGS. 6A-6C are high-level functional schematic drawings of severalactuator mechanisms that can be used with the fluid delivery systememploying the hydraulic pump, according to one embodiment of theinvention.

FIG. 7 is a high-level functional schematic drawing of the adjustablecontrol for aperture opening size.

FIGS. 8A-8B are a high-level functional schematic drawings of severalfluid delivery system with multiple actuators, according to oneembodiment of the invention.

The use of the same reference symbols in different drawings indicatessimilar or identical items.

DETAILED DESCRIPTION

Described herein is a drug delivery system, uses thereof and methods formaking the same. In one embodiment, the systems described herein providepump devices for delivering a medicant, agent, fluid or some othermaterial to a patient, typically through the skin. To this end, thesystem includes an actuator that operates on a reservoir of viscousfluid. The actuator causes the viscous fluid to apply pressure to themedicant being delivered. The viscous fluid is controlled by arestrictor that, in one practice, controls the rate of flow of the fluidso that an uneven application of pressure to the reservoir is mediated,and a controlled rate of fluid movement is achieved. This controlledrate of fluid movement is employed to cause a medicant to be deliveredat a selected rate.

In one embodiment the systems and methods described herein include ahydraulic pump system that may include a chamber (the “pump chamber”)that can be filled with high viscosity fluid, which, when forced bypressure, enters the pump chamber through a restrictor, for example anopening/aperture, which is dimensionally adapted to control the rate offluid flow therethrough. In one embodiment, the aperture is about thesize of a 1-100 μm diameter circle (but not necessarily circular inshape). However, those of skill in the art will understand that anysuitable restrictor may be employed, and that the size and the shape ofthe restrictor can vary to achieve the desired flow rate of the fluidbeing mediated under the expected conditions, including temperature andambient pressure.

The increase in volume of the working fluid inside the pump chambertriggers the movement of a barrier mechanism, which can be coupled toother devices, such as a second (fluid storage) chamber.

One advantage of the instant hydraulic pump system resides with therestrictor through which the high viscosity working fluid flows. Forexample, when the restrictor is an aperture, when subjected to varyingpressure, the working fluid enters the chamber through the aperture at aslow, yet relatively constant rate, thus mostly eliminating thepotentially large variations in the force generating the pressure, whileensuring a substantially less variable expansion in volume of theworking fluid in the chamber. This in turn leads to a relatively smoothand constant movement of the coupled barrier mechanism.

An additional advantage of the hydraulic pump system is that itsrelatively low requirement for a constant pressure source, or its highability to tolerate relatively large variations in force generated bythe pressure source. This is especially useful in manufacturing simpleand inexpensive devices, such as single-use, disposable devices formedical use.

Partly because of the over-pressure employed in the hydraulic pumpsystem, a further advantage is that the hydraulic pump is relativelyinsensitive to environmental changes, such as ambient temperature,altitude, or external pressure.

An illustrative embodiment of the hydraulic fluid system describedherein is shown in the high-level functional drawing of FIG. 1. The pumpchamber 110 may be shaped like, but is not limited to, a cylinder. Thehatched lines represent a moveable barrier 130, which may (but need not(o) be at the distal end of aperture 152. Hydraulic fluid 112 entersaperture 152 on pump chamber wall 150 into pump chamber 110, optionallyvia a connective passage 116.

As used herein, the term “ultrapure” is understood to encompass,although not be limited to, a fluid wherein the largest insolubleimpurity particle in the working fluid is smaller than the aperture size(which may be for example about 2-3 μm in diameter, but could be smalleror larger, and may be adjustable). In those embodiments wherein therestrictor is an aperture, the aperture need not be circular in shape,and could be an oval, a square, a rectangle, a triangle, a polygon, orirregular in shape. In those embodiments wherein the restrictor is atube, valve, sieve, or other mechanism or combination of mechanisms, thesize and shape of the restrictor may be determined empirically bytesting the fluid flow of selected fluids at conditions of interest. Inone particular embodiment, the largest impurity particle is no more than1 mm in diameter, or no more than 500 nm in diameter, or no more than100 nm in diameter. In addition, the total amount of insoluble impurityparticle is less than 0.1%, or 0.01%, or 0.001% in volume.

Viscosity is ordinarily expressed in terms of the time required for astandard quantity of the fluid at a certain temperature to flow througha standard orifice. The higher the value, the more viscous the fluid.Since viscosity varies inversely with temperature, its value is lessmeaningful unless accompanied by the temperature at which it isdetermined. As used herein, “high viscosity” means the working fluid hasa viscosity grade of at least about ISO VG 20, or at least about ISO VG32, or at least about ISO VG 50, or at least about ISO VG 150, or atleast about ISO VG 450, or at least about ISO VG 1000, or at least aboutISO VG 1500.

The hydraulic pump system can be employed in a fluid delivery systemthat can be manufactured inexpensively, and could take advantage of theslow, yet relatively constant delivery rate associated with thehydraulic pump system. Partly due to the slow rate of delivery, thefluid delivery system can be used to continuously deliver a fluid over along period of time, e.g. 6 hrs, 12 hrs, 1 clay, 3 days, 5 days, 10days, one month, etc. The fluid delivery system comprises the hydraulicpump, coupled to a separate chamber for storing fluid to be delivered(the “fluid storage chamber” or “fluid chamber” in short). There couldbe various mechanisms coupling the movement of the barrier mechanism inthe hydraulic pump to the fluid chamber, such that a small amount offluid (ideally equal to, or at least proportional to the amount of theworking fluid entering the hydraulic pump chamber) is expelled from thefluid chamber, through one or more orifice, in response to the movementof the barrier.

One embodiment of the fluid delivery system is illustrated in ahigh-level schematic drawing in FIG. 2 (see detailed description below).This type of fluid delivery system/device can be used for a broad rangeof applications, including but are not limited to biomedical research(e.g. microinjection into cells, nuclear or organelle transplantation,isolation of single cells or hybridomas, etc.), and clinicalapplications (administration of medicaments, etc.).

For example, to provide a low level or variable dose of medicine over along period of time (e.g., hours or even days), the fluid deliverysystem may form a portion of a single-use dispenser for a medicament tobe applied through any of the standard infusions sets available on themarket today or likely to be available in the future. The fluid deliverysystem, formed in some embodiments as low-cost plastic parts, maycomprise a hydraulic cylinder containing two chambers, one function asthe pump chamber described above, the other the fluid chamber forstoring medicaments. In those embodiments, the hydraulic cylinder may beconfigured similarly to most conventional hydraulic cylinders, and thewall, especially the inner wall of at least the chamber for storing aliquid medicament to be delivered, may be composed of bio-inert andinexpensive materials.

The following description is for principal illustration only and shouldnot be construed as limiting in any respect. Various illustrativealternative embodiments are described further below.

Hydraulic cylinder 100, as described in FIG. 2, consists of twochambers, 110 and 120. Chamber 110 (corresponding to the pump chamber)is filled by hydraulic working fluid 112 from a hydraulic reservoir 114.Filling is accomplished by means of a connective passage 116, such as(but not limited to) a tube or lumen either flexibly or rigidlyconnecting hydraulic reservoir 114 and hydraulic cylinder 100. Ashydraulic fluid 112 is forced out of reservoir 114 by actuator 135(consisting, in an exemplary embodiment, of peristaltic compressionplates 135A and 135B and hinge 135C), chamber 110 fills with hydraulicfluid expanding its volume and thus forcing piston element 130 (barriermechanism) into chamber 120 (corresponding to the fluid chamber). Thedotted lines in the actuator and the piston in FIG. 2 represent thelater-in-time position of a plate-hinge actuating mechanism, and thelater-in-time position of the barrier/piston.

FIGS. 3A-3B are schematic diagrams illustrating one advantage of thefluid delivery system, e.g., its ability to tolerate relatively largevariations in force generating the over-pressure, to create a relativelyconstant fluid delivery rate over time or distance traveled by thebarrier piston. It is apparent that without the hydraulic pump system,any direct use of force to expel fluid in the fluid chamber will be hardto control, and will be subjected to a large variation in delivery rateof the fluid (FIG. 3A). In contrast, with the hydraulic pump, thedelivery rate is much more constant (FIG. 3B).

Chambers 110 and 120 can be, but are not necessarily separate, physicalchambers, since both chambers can exist within the confines of ahydraulic cylinder such as the one in FIG. 2 (hydraulic cylinder 100).The chambers are separated by a moveable barrier, such as the pistonelement 130 in FIG. 2, where piston 130 may be a fluid-tight barrierthat prevents hydraulic fluid 112 from entering the second medicamentfluid storage chamber 120. However, the invention is not limited in thetype of hydraulic cylinder 100 or the contours, dimensions or finishesof the interior surfaces of cylinder 100, chamber 110, or chamber 120.Furthermore, the invention is not limited to particular configurationsof piston element 130. The following description illustrates several ofmany possible alternative embodiments that can be employed in thesubject fluid delivery system.

In one embodiment, as shown in FIG. 4A, the piston element 130 in FIG. 2is replaced by a flexible membrane 132 separating the pump chamber 110and the fluid chamber 120. The flexible membrane can expand in responseto the increased pressure from the pump chamber 110, due to the increasein volume of the working fluid entering the pump chamber 110 throughaperture 152. This in turn expels fluid from the fluid chamber 120 viaorifice 140.

In another embodiment, as shown in FIG. 4B, chambers 110 and 120 mayeach have a separate wall unit 134 and 136, respectively (such asexpandable bags made from flexible materials). By virtue of being withinthe limited confinement of cylinder 100, the expansion in volume ofchamber 110 necessarily leads to the decrease in volume of chamber 120,creating a force to expel liquid from chamber 120 via orifice 140.

In yet another embodiment, as shown in FIG. 4C, the pump chamber 110 andthe fluid chamber 120 may be separated from each other, but aremechanically coupled through a barrier mechanism 138 that transmitsmovements in pump chamber 110 to that in the fluid chamber 120. Thecoupling mechanism 138 can either augment or diminish the magnitude ofthe initial movement in the pump chamber 110, such that thecorresponding movement in the fluid chamber 120 is increased, ordecreased, respectively, resulting in expelling a larger or smalleramount of medicament fluid from the fluid chamber 120. For example, thecoupling mechanism 138 can be two pistons linked by a shaft, as shown inFIG. 4C. In one embodiment, the fluid chamber 120 may be detached fromthe pump chamber 110, so that a new fluid chamber (120′, not shown) maybe re-attached.

As noted above, chamber 120 is to be initially filled with a quantity ofliquid component to be delivered, such as a medicament. In the case of amedicament, the quantity would typically be determined by a medicalprofessional in order to provide the necessary dosing over apre-determined period of time. The volume of the fluid chamber may beabout 100 μl, 500 μl, 1 ml, 3 ml, 5 ml, 10 ml, 30 ml, 50 ml, 100 ml ormore.

The depicted hydraulic cylinder 100 in FIG. 2 can be further connectedto an infusion set 160 through orifice 140 at the distal end of chamber120 (distal here meaning the end of chamber 120 distant from piston130). In other words, the output orifice 140 of hydraulic cylinder 100is on the opposite end of the cylinder from hydraulic fluid inputaperture 152, as one would commonly expect in a hydraulic system.However, this is merely one of the preferred designs. The output orifice140 could be located on the wall of cylinder 100 at the chamber 120portion if desired (see FIG. 5 below).

Attached to orifice 140, in some embodiments, is an infusion device or“set” 160 selected from any of the infusion means conventionally knownand used in the medical arts. Examples of infusion devices include: aneedle, such as depicted in FIG. 1; a lumen and needle set; acatheter-cannula set; or a microneedle or microneedle array attached bymeans of one or more lumens. One of ordinary skill in the art willreadily appreciate that many devices exist to convey medicaments into abody. Accordingly, the invention is not limited in the types of infusionor injection devices used therewith.

In an illustrative embodiment, as shown here in a high-level schematicdrawing in FIG. 5, the fluid delivery system is affixed to a deliveryarea of a patient, e.g. skin 200, by an adhesive means, such as atransdermal patch. The fluid chamber 120 is connected to a microneedleor an array of microneedles 180, such as those described in U.S. Pat.No. 6,503,231 (incorporated herein by reference). Unlike what is shownin FIG. 5, the microneedle(s) need not completely enter the skin layer200. To achieve a low profile, both the pump chamber 110 and the fluidchamber 120 may be flat in shape (rather than shaped like a cylinder),and the outer-surfaces may hug the contour of the attached skin layer200. The orifice(s) (not shown) connecting the fluid chamber and themicroneedle(s) preferably opens on a side-wall of the fluid chamber 120.Alternatively, a connective passage may link the orifice on fluidchamber 120 to the microneedle or microneedle(s) array. Barrier 130 andaperture 152 are as described above. Also shown is one embodiment of theactuator, where plates 135 actuated by spring mechanism squeeze thehydraulic fluid reservoir 114 to inject hydraulic working fluid into thepump chamber 110. Other actuators, such as those described in otherparts of the specification, may be adapted for use in this embodiment.

As exemplified in FIG. 2, in operation, the fluid (e.g. medicament) isadministered by compressing hydraulic fluid reservoir 114 in acontrolled manner with actuator 135. FIG. 2 shows an exemplaryperistaltic mechanism actuator 135. However, the actuator may bealternatively selected from any of a number of squeeze devices thatapply a force on the reservoir, such as a miniaturized bellows crank orpaired rollers bearing on reservoir 114 (see FIG. 6 below). Moreover, inother embodiments, the reservoir can be acted on by an expanding gasvolume, thermal energy, or any other device or process that will becapable of causing the fluid to apply a pressure, either directly orindirectly, to the medicant being delivered.

In the embodiment shown in FIG. 2, plates 135A and 135B are attached byhinge 135C and forced together by means of a spring or, in someembodiments, one or more piezoelectric elements, such that flexible(e.g., elastomeric) hydraulic fluid reservoir 114 is squeezed betweenthem. Squeezing an elastomeric reservoir forces the contents of thereservoir out through whatever aperture exists in the reservoir. In someembodiments, an aperture 152 is provided by the coupling tube 116 andthe adjustable aperture 150, further described below.

Actuator 135 may also take on other forms. Ratchet or stepper motordriven units that compress plates or other structures bearing onhydraulic reservoir 114 that move hydraulic fluid may also be usedwithout departing from the present invention. Additionally, for atwo-plate hinged peristaltic mechanism such as that represented byreference designator 135 in FIG. 2, springs mounted internally orexternally to the plates (not shown) may be used to force the platestogether. Electrically driven or piezoelectric mechanisms, such as thosedescribed in the prior art, may also be employed.

In one embodiment, as shown in FIG. 6A, one or more external spring(s)135D having a constant spring coefficient over its full range of motionis (are) employed, (For the sake of simplicity, a single springconfiguration is described. But multiple springs may be used to adjustforces.) This spring is disposed so as to connect portions of plates135A and 135B distant from hinge 135C and to draw them together(inwardly), thus bearing on reservoir 114. Thus, when the system isinitially prepared for use, the spring is extended (i.e., placed intension) by forcing plates 135A and 135B apart. The plates are then heldin place with a removable brace or other device (not shown) to keep themfrom compressing hydraulic reservoir 114. Once the pump is in place andconnected through infusion means 160 (see FIG. 2, but not shown here) toinject the medicament into the patient, the brace may be removed. Theconstant spring tension placed on plates 135A and 135B of actuator 135will then slowly force the plates together and squeeze hydraulic fluid112 out of reservoir 114 in a peristalsis-like action.

In another embodiment, as illustrated in FIG. 6B, a compressed spring orset of springs 260 may be used to push a piston element 250 through aguided-path to compress the hydraulic fluid reservoir 114. At the end ofthe reservoir, distal to the piston element 250, is an aperture 152 thatallows the hydraulic fluid 112 to enter the adjacent pump chamber 110,so that barrier 130 may move accordingly. In a more simplified version,the spring mechanism 250 and 260 may be replaced by thumb force 300,just like in a traditional syringe (FIG. 6C). In both FIGS. 6B and 6C,there is no connective passage separating the fluid reservoir 114 fromthe pump chamber 110.

The adjustable aperture provides regulation of the hydraulic pressureand flow rate in the pump chamber 110. This regulation may be effectedby allowing the aperture 152 (in FIG. 2) to be adjusted to extremelysmall dimensions, for example, to a diameter of one-ten thousandths ofan inch (0.0001 inches, or about 2.5 μm) or less.

In one embodiment, the aperture 152 has a fixed size. It does not haveto be round/circular in shape. For example, it could be roughly asquare, a triangle, an oval, an irregular shape, or a polygon. Whateverthe shape, the area of the opening will be sized to achieve the flowrate desired. In example, the opening may be about one-tenth thousandthsof an inch (or 2-3 μm) in diameter. Depending on use, the opening sizecan be anything, including an opening between 200 nm-500 nm, or 500nm-1000 nm, or 1-2 μm, or 5-10 μm. Other sizes and dimensions can beselected and the size and dimension selected will depend upon theapplication at hand.

In other embodiments, as shown in FIG. 7, the aperture 152 may beadjustable in size, as by means of a conventional iris mechanism (seeFIG. 7), miniature valve, or paired gating slits (for example and not byway of limitation) currently known in the arts. For example, theadjustable aperture 152 may be adjusted by means of a simple thumb wheel150 that activates the conventional, miniaturized valve or iris devicediscussed above. In an alternate embodiment, an electrical motor orpiezoelectric device may be used to open or close the aperture, thusaffecting the rate at which hydraulic fluid 112 flows into chamber 110and moves barrier 130.

Regardless of whether the aperture is adjustable or not, the flow rateof the hydraulic fluid can be controlled to suit different needs. Incertain embodiments, the quantity of the fluid in the fluid chamber isexpelled at a rate selected from: about 100 nl-1 μl per minute, about1-10 μl per minute, or about 10-100 μl per minute. In other embodiments,the fluid rate is mediated and controlled to be from 0.001 μl per hourto 100 milliliters per hour. The rate selected will depend upon theapplication at hand, and those of skill in the art will be able todetermine the proper dosage rate for a given application.

One feature of aperture 152, whether adjustable or not, is that it canbe made extremely small so that hydraulic fluid 112 enters chamber 110at very low rates, such as but not limited to rates as low as ones ortens of micro-liters per minute. When used with a hydraulic fluid ofappropriate viscosity (further discussed below), the configuration ofaperture 152 enables precise pressure regulation that is insensitive toambient pressure or other environmental conditions. This insensitivity,in turns, allows for highly accurate dosing and dose regulation under awider range of conditions than previously seen in the arts.

Hydraulic fluid 112 is, in some embodiments, an ultrapure, highviscosity, bio-inert material. Viscosity is limited at its upper boundby the amount of force developed by the actuator. In certainembodiments, the force generated by the actuator is about 10 lb, 5 lb, 3lb, 2 lb, 1 lb, 0.5 lb, 0.1 lb, 0.001 lb or less. At its lower bound,the fluid must be viscous enough so that the flow can remain highlyregulated by the combination of actuator pressure and aperture diameterin all environment conditions, especially in the presence of lowatmospheric pressure and/or high ambient temperature (where viscositytends to decrease). A simple test may be performed to roughly determinethe average flow rate of the hydraulic fluid, by fixing an aperture sizeand the pushing force exerted on the fluid reservoir, and determiningthe amount of hydraulic fluid remaining in the reservoir (and thus theamount exited) after a period of time. Consecutive periods of hydraulicfluid loss (e.g. fluid loss in consecutive 5-minute periods, etc.) maybe measured to determine if the rate of hydraulic fluid loss from thereservoir is constant over time under the condition used.

Medicaments suitable for use with the system presently disclosedinclude: insulin, opiates and/or other palliatives, hormones,psychotropic therapeutic composition, or any other drug or chemicalwhose continuous low volume dosing is desirable or efficacious for usein treating patients. Note too that “patients” can be human or non-humananimal; the use of continuous dosing pumps is not confined solely tohuman medicine, but can be equally applied to veterinarian medicines.

In an alternate embodiment of the system, two or more hydraulicreservoirs and actuators are provided (FIGS. 8A-8B). In an illustrativeembodiment shown in FIG. 8A, the first reservoir 400 and actuator 235are the same as or similar to items 114 and 135 in FIG. 2. The secondreservoir 500 and actuator 235, which may use the same peristalticactuator 135 as shown in FIG. 2 or any other conventional alternative,such as those described above, are provided with a separate control. Inother words, the second actuator may be controlled independently of thefirst. Both fluid reservoirs are connected to the pump chamber wall 150,through apertures 154 and 156, respectively. The connection mayoptionally go through connective passages 116. Such a configuration isuseful in situations where special, discrete doses of the medicament maybe necessary. For example, an insulin-dependent diabetic may often findit necessary to receive an additional booster dose or bolus of insulinimmediately after meals, in addition to and along with continuouslysupplied insulin during the day. The second actuator control may thus beoperated independently of the first actuator control mechanism todeliver the bolus.

In an alternative embodiment, shown in FIG. 8B, hydraulic fluid 112 fromboth reservoirs 400 and 500 may pass together through a common lumen 116and thence through adjustable aperture 152 (FIG. 8B). Alternatively, asdescribed above, the two reservoirs may lead into hydraulic chamber 110by way of separate lumens and separately adjustable apertures 154 and156 (FIG. 8A). In this latter configuration, the rate of dosing affectedby either reservoir may be independently controlled through theirrespective adjustable apertures.

In a further alternative, one of the reservoirs may lead to a fixedaperture while the other leads to an adjustable aperture. In thisembodiment, useful in cases such as the insulin-dependent diabeticdescribed above, the fixed-aperture-connected hydraulic reservoir can beactuated to provide bolus dosing at discrete intervals, while theadjustable-aperture-connected hydraulic reservoir can be used to providecontinuous slow dosing.

Exemplary Embodiment of Using the Fluid Delivery System

In one exemplary embodiment, there is provided a method of administeringa medicament, comprising: compressing a hydraulic fluid reservoir toforce said hydraulic fluid through a connection means; passing saidhydraulic fluid through an adjustable aperture into a first, pumpchamber, wherein said pump chamber is separated from an adjacent fluidstorage chamber, for example, by a moveable barrier, and wherein saidfluid storage chamber is filled with a medicament; displacing saidmoveable barrier into said fluid storage chamber by filling said pumpchamber with said hydraulic fluid, wherein said displacing causes aquantity of said medicament to be expelled from said fluid storagechamber through an orifice.

Said passing may be regulated by said adjustable aperture varying theflow of said hydraulic fluid and thus the quantity of said medicamentexpelled through said orifice. Furthermore, the method may furthercomprise injecting a quantity of said medicament into a patient throughan infusion set connected to said orifice.

In some embodiments, the step of compressing may employ peristalticcompaction of said reservoir at a constant rate. Alternatively, thecompressing step may employ peristaltic compaction of said reservoir ata variable rate.

In yet another alternate embodiment, the method may further compriserapidly compressing a second hydraulic reservoir fluidly connected tosaid pump chamber to displace said moveable barrier and thus cause abolus of said medicament to be expelled through said orifice. Thisembodiment may further comprise passing said hydraulic fluid from saidsecond hydraulic reservoir through a second aperture into said pumpchamber.

Alternate Embodiments

The order in which the steps of the present method are performed ispurely illustrative in nature, and the steps may not need to beperformed in the exact sequence they are described. In fact, the stepscan be performed in any suitable order or in parallel, unless otherwiseindicated as inappropriate by the present disclosure.

While several illustrative embodiments of the hydraulic pump system andits use in the fluid delivery system have been shown and described, itwill be apparent to those skilled in the art that changes andmodifications may be made without departing from this invention in itsbroader aspect and, therefore, the appended claims are to encompasswithin their scope all such changes and modifications as fall within thetrue spirit of this invention.

1. A hydraulically actuated fluid delivery system for sustained deliveryof a liquid component, comprising: a pump chamber, and a fluid storagechamber having an orifice and being functionally connected to said pumpby a moveable barrier; a hydraulic fluid reservoir for storing a highviscosity fluid, said reservoir being connected to said pump chamber viaa restrictor capable of controlling the rate of flow of the highviscosity fluid, and an actuator functionally connected to saidhydraulic fluid reservoir to cause said hydraulic fluid to flow intosaid pump chamber through said restrictor, thereby expanding the volumeof said pump chamber, displacing said moveable barrier and causing aquantity of said liquid component stored in said fluid storage chamberto be delivered at a sustained rate.